Progression-Free Survival (PFS) based on Response Evaluation Criterion in Solid Tumors [RECIST] version 1.1 (documented by independent radiology laboratory) [ Time Frame: From randomization to date of first documentation of objective tumor progression or death due to any cause, whichever occurs first. Follow-up will continue for 18 months after last patient is randomized or until required number of PFS events is observed. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Objective Response Rate (ORR) (confirmed by independent radiology review) [ Time Frame: From randomization to complete response (CR) or partial response (PR). Up to 18 months follow-up or until required number of PFS events is observed. ] [ Designated as safety issue: No ]

Duration of Response (DR) [ Time Frame: From first documentation of objective tumor response (CR or PR) to first documentation of objective tumor progression or to death. Up to 18 months follow-up or until required number of PFS events is observed. ] [ Designated as safety issue: No ]

Overall Survival (OS) [ Time Frame: From randomization to the date of death due to any cause. Follow-up will continue until death or 36 months after the randomization of the last patient. ] [ Designated as safety issue: No ]

Time To Deterioration (TTD) [ Time Frame: From randomization to deterioration while on study treatment. Up to 18 months follow-up or until required number of PFS events is observed. ] [ Designated as safety issue: No ]

Health Related Quality of Life (HRQoL) [ Time Frame: Cycle 1 day 1 to end of treatment or withdrawal or crossover. ] [ Designated as safety issue: No ]

Time To Progression (TTP) [ Time Frame: From the date of randomization to the date of the first documentation of objective tumor progression. Up to 18 months follow-up or until required number of PFS events is observed. ] [ Designated as safety issue: No ]

Intracranial Time To Progression (IC-TTP) [ Time Frame: From the date of randomization to the date of the first documentation of objective tumor progression but only considering intracranial disease. Up to 18 months follow-up or until required number of PFS events is observed. ] [ Designated as safety issue: No ]

Extracranial Time To Progression (EC-TTP) [ Time Frame: From the date of randomization to the date of the first documentation of objective tumor progression but only considering extracranial disease. Up to 18 months follow-up or until required number of PFS events is observed. ] [ Designated as safety issue: No ]

Survival Probabilities [ Time Frame: At 1 year and at 18 months, after the date of randomization. ] [ Designated as safety issue: No ]

Disease Control Rate (DCR) [ Time Frame: At 12 weeks, after the date of randomization. Up to 18 months follow-up or until required number of PFS events is observed. ] [ Designated as safety issue: No ]

Time to Tumor Response (TTR) [ Time Frame: From randomization to the date of the first documentation of objective tumor progression. Up to 18 months follow-up or until required number of PFS events is observed. ] [ Designated as safety issue: No ]

250 mg two times daily [BID], oral, on a continuous daily dosing schedule. Cycles are defined in 21 day periods.

Active Comparator: Chemotherapy

Chemotherapy [Option at Investigator's Choice]

Drug: Pemetrexed/Cisplatin

Option 1: Pemetrexed/Cisplatin; Pemetrexed, 500 mg/m^2, will be administered by intravenous infusion over 10 minutes or according to institutional administration timing on Day 1 of a 21-day cycle. Cisplatin, 75 mg/m^2 will be administered by infusion after adequate hydration according to institutional practices beginning approximately 30 minutes after the end of the pemetrexed infusion. Pemetrexed and cisplatin will be repeated every 3 weeks for a maximum of 6 cycles.

Drug: Pemetrexed/Carboplatin

Option 2: Pemetrexed/Carboplatin. Pemetrexed, 500 mg/m^2, will be administered by intravenous infusion over 10 minutes or according to institutional administration timing on Day 1 of a 21-day cycle. Carboplatin, at a dose calculated to produce an AUC of 5 or 6 mg.min/mL will be administered by infusion according to institutional practices beginning approximately 30 minutes after the end of the pemetrexed infusion. Pemetrexed and carboplatin will be repeated every 3 weeks for a maximum of 6 cycles.

Eligibility

Ages Eligible for Study:

18 Years to 70 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Histologically or cytologically proven diagnosis of locally advanced not suitable for local treatment, recurrent and metastatic non-squamous cell carcinoma of the lung.

No prior systemic treatment for locally advanced or metastatic disease. Patients with brain metastases only if treated and neurologically stable for at least 2 weeks and are not taking any medications contraindicated in Exclusion Criteria

Evidence of a personally signed and dated informed consent document and willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures including completion of patient reported outcome [PRO] measures.

Use of drugs or foods that are known potent CYP3A inducers/inhibitors Concurrent use of drugs that are CYP3A substrates with narrow therapeutic indices.

Known HIV infection

History of extensive disseminated/bilateral or known presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis, but not history of prior radiation pneumonitis.

Other severe acute or chronic medical conditions (including severe gastrointestinal conditions such as diarrhea or ulcer) or psychiatric conditions, or end-stage renal disease on hemodialysis, or laboratory abnormalities that would impart, in the judgment of the investigator and/or sponsor, excess risk associated with study participation or study drug administration, and which would, therefore, make the patient inappropriate for entry into this study.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01639001